The proposed project will develop methods for noninvasive evaluation of the early stages of atherogenesis, using nuclear magnetic resonance (NMR) imaging and special methods of image processing. The significance of this proposed research lies in the vital importance of identifying atheroma formation at reversible stages, and of quantifying the disease state non-invasively. Atherogenesis, if unchecked, leads to arteriosclerosis, the leading cause of death and debility in the United States. This proposed research develops a new and unique approach which is based on recent discoveries by the applicant about the nature of and physicochemical basis for a specific NMR signal from atheroma, addressable by a multidimensional approach to NMR imaging. The primary objectives of this project are: 1) development of multidimensional NMR imaging methods for use in the evaluation of early atheromatous disease in different size blood vessels in both a rabbit model of atherogenesis and in clinical patients, and 2) development of an investigational form, NMR microscopy, to address basic science questions about the disease process, by allowing non-perturbing serial microscopic observation of the disease evolution in rabbits. For each of these goals, extensive work is planned to 1) test and refine the methods for the in vivo applications, 2) validate the methods in vitro, and 3) validate the methods in vivo. This is a comprehensive five-year proposal, with validation on both animal models and human volunteers, to provide an accurate means for evaluating directly but noninvasively the effects of interventions aimed to halt or reverse the disease which currently claims the lives of over 550,000 Americans per year.